[Hip fractures in patients treated with antipsychotic drugs. Study of retrospective cohorts in Catalonia]. / Fracturas de cadera en pacientes tratados con fármacos antipsicóticos. Estudio de cohortes históricas en Cataluña.

OBJECTIVE: To evaluate the incidence of hip fracture in patients with antipsychotic treatment, comparing it with that of individuals who have not been treated with antipsychotics. DESIGN: Retrospective cohort study of patients treated with antipsychotic drugs (TAP) and patients without known treatment (non-TAP). The observation period was 2006-2014. SITE: All primary care teams in Catalonia of the Catalan Health Institute (ICS). PARTICIPANTS: Patients older than 44 years with TAP lasting at least 3 months. Control cohort: random selection of non-TAP patients matching for baseline comorbidities and other variables. A total of 22,010 are analyzed. Main measurements Incidence rate (1000× person-years: PY) of hip fracture in each group (TAP and non-TAP). Cox regression models to estimate adjusted risks (hazard ratio: HR). RESULTS: The hip fracture incidence rate was higher in TAP patients (5.83 vs 3.58 fractures per 1000 PY), and is higher in all strata according to sex, age and type of diagnosis. The risk of suffering a hip fracture was 60% higher (HR: 1.60 95% CI: 1.34-1.92) in the TAP group than in the non-TAP group. The risk was higher in the group with schizophrenia (HR: 3.57 95% CI: 1.75-7.30), followed by bipolar disorder (HR: 2.61; 95% CI: 1.39-4.92) and depression (HR: 1.51; 95% CI: 1.21-1.88). CONCLUSIONS: Patients with antipsychotic treatment have a higher risk of hip fracture than those who have not been treated with antipsychotics.

Rotavirus gastroenteritis hospitalizations in provinces with different vaccination coverage rates in Spain, 2013-2018.

BACKGROUND: Rotavirus (RV) vaccines are available in Spain since 2006 but are not included in the National Immunization Program. RV vaccination has reached an intermediate vaccination coverage rate (VCR) but with substantial differences between provinces. The aim of this study was to assess the ratio of RV gastroenteritis (RVGE) admissions to all-cause hospitalizations in children under 5 years of age in areas with different VCR. METHODS: Observational, multicenter, cross-sectional, medical record-based study. All children admitted to the study hospitals with a RVGE confirmed diagnosis during a 5-year period were selected. The annual ratio of RVGE to the total number of all-cause hospitalizations in children < 5 years of age were calculated. The proportion of RVGE hospitalizations were compared in areas with low (< 30%), intermediate (31-59%) and high (> 60%) VCR. RESULTS: From June 2013 to May 2018, data from 1731 RVGE hospitalizations (16.47% of which were nosocomial) were collected from the 12 study hospitals. RVGE hospital admissions accounted for 2.82% (95 CI 2.72-3.00) and 43.84% (95% CI 40.53-47.21) of all-cause and Acute Gastroenteritis (AGE) hospitalizations in children under 5 years of age, respectively. The likelihood of hospitalization due to RVGE was 56% (IC95%, 51-61%) and 27% (IC95%, 18-35%) lower in areas with high and intermediate VCR, respectively, compared to the low VCR areas. CONCLUSIONS: RVGE hospitalization ratios are highly dependent on the RV VCR. Increasing VCR in areas with intermediate and low coverage rates would significantly reduce the severe burden of RVGE that requires hospital management in Spain. Clinical trial registration Not applicable.

Proper pertussis vaccination will probably not increase vaccination coverage: a case-control study.

Vaccination coverage (VC) against pertussis can increase when management practices and policies at primary care centres (PCCs) are reinforced. From 2011 to 2015, we performed a case-control study to evaluate VC among pertussis patients treated at PCCs in Barcelona, Spain. We recorded pertussis in patients from 8- to 16-year-olds at 52 PCCs. Pertussis cases had laboratory diagnostic and controls were healthy outpatients visiting the same facility for reasons other than cough. DTaP/dTap VC was recorded as either proper vaccination status (five doses recorded) or improper vaccination status (<5 doses recorded). We used a logistic regression model to estimate OR and 95% CI. We included 229 cases and 576 controls. VC was higher in cases (mean 5.01, s.e.: 0.57) than in controls (4.89, s.e.: 0.73). Around 69% of the cases had received DTaP primary immunisation after 2-5 years and 31.4% of cases had the dTap booster immunisation after 7-10 years. The 87% of children 5-9 years were properly vaccinated. We found no protection from becoming ill among properly vaccinated children (OR 1.87; 95% CI 1.22-2.85). The highest VC was observed in patients with confirmed pertussis, which was likely due to a more exhaustive follow-up of the VC in these patients. Being properly vaccinated against pertussis will probably not increase VC.

Understanding nitrogen recovery from wastewater with a high nitrogen concentration using microbial electrolysis cells.

This study was aimed at understanding the effect of applied voltage, catholyte and reactor scale on nitrogen recovery from two different organic wastes (digestate and pig slurry) by means of microbial electrolysis cell (MEC) technology. For this purpose, MEC sizes of 100, 500 and 1000 mL were tested at applied voltages of 0.6, 1 and 1.4 V using either a phosphate-buffered solution or NaCl solution as the catholyte. By increasing the reactor size from 500 to 1000 mL, a decrease in the ammonia recovery efficiency from 47 to 42% was observed. The results also showed that the phosphate-buffered solution is preferable as the catholyte and that the voltage applied does not have a noticeable effect on current production and ammonia recovery. Low biodegradability of the wastes was identified as the main bottleneck.

[Image-guided brachyablation for hepatocarcinoma. Report of one case]. / Image-Guided BrachyAblation (IGBA) en hepatocarcinoma. Descripción de la técnica y reporte del primer caso en Chile.

Eighty percent of hepatocarcinomas are inoperable at the moment of diagnosis. Liver transplantation is the treatment of choice in these cases, but local therapies are another alternative. Among these, Image-Guided BrachyAblation is a safe choice. We report a 76-year-old male with a hepatocarcinoma, who was considered inoperable due to the high surgical risk of the patient. A local treatment with Image-Guided BrachyAblation was decided. A brachytherapy needle was placed in the tumor under computed tomography guidance and a 15 Gy single dose was delivered from an Iridium-192 source. The patient had no immediate complications and at one month of follow up he continued without incidents.

Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain.

BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS.

Multicenter prospective study on the burden of rotavirus gastroenteritis in children less than 3 years of age in Spain.

BACKGROUND: Rotavirus is acknowledged as an important cause of paediatric gastroenteritis worldwide. In Spain, comprehensive data on the burden of rotavirus disease was lacking. METHODS: A prospective, multicenter, observational study was carried out, during the winter season, from October to April 2014 in selected areas of Spain (Catalonia, Basque Country, Andalusia) to estimate the frequency and characteristics of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children ≤3 years of age seeking medical care in primary care and emergency department centres. RESULTS: Of the 1087 episodes of AGE registered, 33.89 % were RVGE positive. The estimated incidence of RVGE, was 40.3 (95 % CI 36.1-44.8) episodes per 10,000 child-months in children ≤ 3 years of age and the 5-month (December-April) seasonal RVGE incidence rate was 2.01 [1.81-2.24] per 100 children. No vaccination and attending a day care centre were the main risk factors for RV infection. RVGE infected children presented more frequently with fever (63.9 % vs. 45.1 %, p = 0.009), vomiting (61.2 % vs. 44.3 %, p = 0.015), suffered more dehydration, and were hospitalised and went to the emergency room more often (41.7 % vs. 15.7 %, p <0.001) than non-RVGE infected ones. Children were usually more tired (77.5 % vs. 54.2 %, p <0.001), tearful, (47.2 % vs. 34.8 %, p <0.001), and easily irritated (76.5 % vs. 59.8 %, p <0.001), and parents were more concerned (41.7 % vs. 15.7 %, p <0.001) and suffered more working rhythm disturbances (39.0 % vs. 22.9 %, p <0.001). The cost for families of RVGE cases was significantly higher than the cost of non-RVGE infected ones (47.3 vs 36.7 euros, p = 0.011). Vaccinated children suffered less clinical symptoms and no hospitalization. Therefore, vaccination decreases the psychosocial stressors caused by the disease in the family. CONCLUSIONS: Rotavirus infections are responsible for a substantial proportion of AGE cases in children ≤3 years of age in Spain attended at primary care visits. RVGE episodes are associated with greater clinical severity, greater alterations in the child´s behaviour, and higher parental distress. The outcomes of the present study recommend that routine rotavirus vaccination in infants ≤3 years of age could considerably reduce the serious burden of this potentially serious childhood disease.

A third subunit in ancestral cytochrome c-dependent nitric oxide reductases.

Reduction of NO to N2O by denitrifiying bacteria is catalyzed either by a monomeric quinol-nitric oxide reductase (qNor) or by a heterodimeric cytochrome c-dependent nitric oxide reductase (cNor). In ancient thermophilic bacteria belonging to the Thermales and Aquificales phylogenetic groups, the cluster encoding the cNor includes a small third gene (norH), in addition to those encoding homologues to the subunits of a typical cNor (norC and norB). We show in Thermus thermophilus that the three genes are cotranscribed in a single mRNA from an inducible promoter. The isolation of individual nor mutants and the production in vivo of His-tagged NorH protein followed by immobilized-metal affinity chromatography (IMAC) allowed us to conclude that NorH constitutes a third subunit of the cNor from T. thermophilus, which is involved in denitrification in vivo, likely allowing more efficient electron transport to cNor.

Spirometric and exhaled nitric oxide reference values in preschool children from the community of Navarra.

BACKGROUND AND OBJECTIVE: Preschool children can perform quality, reproducible spirometric maneuvers, provided appropriate equipment is used and specially trained nursing staff training are available. However, use of spirometry for the diagnosis and follow-up of preschool children with respiratory diseases remains limited in clinical practice, because consensus on test quality and acceptability criteria and reference data are lacking. We initiated the present study with the aim of developing reference equations, since tables of normal values for this age group are not available in our area. PATIENTS AND METHODS: The study population comprised healthy preschool children in our community. Normal values for exhaled nitric oxide in this age range were assessed. Regression equations were constructed using univariate and multivariate models. RESULTS: A total of 114 healthy preschool children aged 3 to 6 years were enrolled. According to the criteria of the American Thoracic Society/European Respiratory Society, 60 children were able to perform acceptable and reproducible spirometric maneuvers. The best correlations were observed for the untransformed linear regression model that included height. The correlation coefficients for forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV0.5 were 0.89, 0.88, and 0.86, respectively. The regression equations for the calculation of reference values were as follows: FVC = -2.6 + 0.036 x height, cm FEV1 = -2.04 + 0.029 x height, cm FEV0.5 = -1.53 + 0.022 x height, cm. We obtained fraction of inhaled nitric oxygen (FeNO) values for 56 children. The mean (SD) value was 11 (4.9) ppb. CONCLUSIONS: Most preschool children in our area were able to perform quality spirometry maneuvers. We obtained regression equations that allowed us to calculate the reference ranges in our population and the distribution of normal FeNO values.

Variability and concordance of Cornell and Sokolow-Lyon electrocardiographic criteria in hypertensive patients.

AIM: To assess the variability and concordance of left ventricular hypertrophy electrocardiographic (LVH-ECG) criteria. METHODS AND RESULTS: Convenience sampling of hypertensive subjects without coronary disease or bundle branch blocks. Two electrocardiograms (ECGs) were performed on each patient. Two investigators carried out two blind-readings of each ECG (Cornell and Sokolow-Lyon criteria). The between-rater and within-rater reliability were assessed (intraclass correlation coefficient, ICC). Poor concordance was defined: mean voltage difference between both ECGs >2 mm; 824 ECG readings were performed in 103 subjects (58.3% females), aged 66.8±8.8 years, mean blood pressure 141±15.10/78±9.0 mmHg. The between-rater ICCs of the baseline ECG were 0.97(95% CI 0.96-0.98) and 0.98 (95% CI 0.97-0.99) for Cornell and Sokolow-Lyon criteria, respectively. Poor concordance was found in 39.8% and in 41.7% of the cases for Cornell and Sokolow-Lyon criteria, respectively. Systolic blood pressure was found to be significant and positively associated with both criteria. Elderly hypertensive subjects, with higher ECG voltages and lower pulse pressure presented poor concordance of Cornell criteria. CONCLUSIONS: The between-rater and within-rater reliability of Cornell and Sokolow-Lyon criteria is minimal. Approximately 40% of hypertensive subjects presented poor concordance in a second ECG. Older patients with lower pulse pressure and higher baseline voltages presented poorer reproducibility of LVH-ECG criteria.

Infectivity study of Streptococcus phocae to seven fish and mammalian cell lines by confocal microscopy.

Streptococcus phocae is a beta-haemolytic bacterium that causes systemic infections in Atlantic salmon, Salmo salar L., cultured in southern Chile and also in seals. In this study, the host-pathogen interaction between S. phocae and seven types of cell lines (fish and mammalian) was examined using an indirect fluorescent antibody and confocal microscopy (CM). Chinook salmon embryo (CHSE-214), epithelioma papulosum cyprini (EPC), salmon head kidney (SHK-1) and Atlantic salmon kidney were used as the fish cell lines, while human cervix epithelial adenocarcinoma (HeLa), African green monkey kidney fibroblast (Cos-7) and mouse leukaemic monocyte macrophage (Raw 264.7) were included as mammalian cell lines. Streptococcus phocae type strain ATCC 51973(T) and isolates LM-08-Sp and P23 were selected as representatives from the salmon and seal host, respectively. For the CM examination, monolayers seeded on round coverslips were studied at 2- and 20-h post-inoculation (pi). The results showed that there is no common infectivity pattern between the three S. phocae strains at 2-h pi and the cell lines tested, regardless of the source of isolation (seal or salmon). All S. phocae strains could internalize and were found inside the fish and mammalian cell cytoplasm after 20-h pi. Regardless of the cells studied (fish or mammal) and incubation (2 and 20 h), S. phocae was never observed inside the nuclei. Seal and salmon isolates showed the highest number of bacteria entering into the primate cell lines (HeLa and Cos-7) from 2-h pi, while ATCC 51973(T) was not found outside or inside the HeLa and Cos-7 cells.

Bioinformatic analysis of the genome of infectious salmon anemia virus associated with outbreaks with high mortality in Chile.

The infectious salmon anemia virus (ISAV), an orthomyxovirus, is the major cause of outbreaks of high mortality rates in salmon in Chile. It has been proposed that the virulence of ISAV isolates lies mainly in hemagglutinin-esterase and fusion glycoproteins. However, based on current information, the contribution of other viral genes cannot be ruled out. To study this, we isolated and determined the complete coding sequence of two high-prevalence Chilean isolates associated with outbreaks of high mortality rates: ISAV752_09 and ISAV901_09. These isolates were compared to 15 Norwegian isolates that exhibit differences in their virulence. For this purpose, we performed bioinformatic analyses of (i) functional domains, (ii) specific mutations, (iii) Bayesian phylogenetics, and (iv) structural comparisons between ISAV and influenza virus glycoproteins by using molecular modeling. Phylogenetic analysis shows two genogroups for each protein, one of them containing the Chilean isolates. The gene sequence of the polymerase complex and nucleoprotein indicated that they are closely related to homologues from highly pathogenic Norwegian viruses. Notably, seven of the eight mutations that are present only in the Chilean isolates are on the polymerase complex and nucleoprotein. Structural modeling of hemagglutinin-esterase shows patches of variable residues on its surface. Fusion protein modeling shows that insertions are flexible regions that could affect proteolytic processing, increasing either the accessibility or the number of recognition sites for specific proteases. We found antigenic drift processes related to insertion into the isolated segment 5 of the ISAV752_09. Our results confirm the European origin of Chilean isolates to be the result of reassortments from Norwegian ancestors.

Potential hypersensitivity due to the food or food additive content of medicinal products in Spain.

The Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology reviewed the allergenic potential of several substances of food origin that are found in the composition of some drugs. Despite recent legislation on labeling, many labels do not clearly state whether the drug contains raw material (active ingredients, excipient, or other manufacturing intermediate) with an origin in any of the substances in the list of the 14 groups of food allergens that are subject to mandatory declaration. The objective of legislation is that the drug package, the Summary of Product Characteristics, and the patient information leaflet clearly state the food content in order to improve the safety of allergic patients. Therefore, any food or allergen derivative that must be declared should be clearly stated on the drug label. Of all the evaluated products, egg and milk derivatives are the most frequently discussed in literature reviews. The natural or synthetic origin of potentially allergenic substances such as lysozyme, casein, lactose, albumin, phosphatide, and aromatic essences should be clearly stated. Providing this information has 2 clear advantages. First, allergic reactions to drugs in patients with food allergy could be avoided (if the substances have a natural origin). Second, prescription would improve by not restricting drugs containing synthetic substances (which do not usually induce allergic reactions).

Strategic noise map of a major road carried out with two environmental prediction software packages.

The main objective of this study is to analyze the differences found in the results of noise mapping using two of the most popular software techniques for the prediction of environmental noise. The location selected to conduct the comparative study is an area encompassed by the ring road that surrounds the city of Pamplona and on a grid, with a total of 6 x 10(5) points, approximately. In fact, and as the Environmental Noise Directive points out, it is a major road designated by a Member State (Spain). Configuration of the calculation parameters (discretization of the sources, ground absorption, reflection order, etc.) was as equivalent as possible as far as programs allow. In spite of that, a great number of differences appear in the findings. Although in 95.5% of the points the difference in the noise level calculated from the two programs was less than 3 dB, this general statistic result concealed some great differences. These are due to the various algorithms that programs implement to evaluate noise levels. Most differences pertain to highly screened receivers or remote ones. In the former, the algorithm of visibility is the main cause of such differences. In the latter, differences are mainly brought about by a different implementation of the propagation under homogeneous and favorable atmospheric conditions from both software systems.

Degradation of 2-mercaptobenzothizaole in microbial electrolysis cells: Intermediates, toxicity, and microbial communities.

The compound 2-mercaptobenzothizaole (MBT) has been frequently detected in wastewater and surface water and is a potential threat to both aquatic organisms and human health (its mutagenic potential has been demonstrated). This study investigated the degradation routes of MBT in the anode of a microbial electrolysis cell (MEC) and the involved microbial communities. The results indicated that graphene-modified anodes promoted the presence of more enriched, developed, and specific communities compared to bare anodes. Moreover, consecutive additions of the OH substituent to the benzene ring of MBT were only detected in the reactor equipped with the graphene-treated electrode. Both phenomena, together with the application of an external voltage, may be related to the larger reduction of biotoxicity observed in the MEC equipped with graphene-modified anodes (46.2 eqtox∙m-3 to 27.9 eqtox∙m-3).

Juvenile Xanthogranuloma: An Entity With a Wide Clinical Spectrum. / Xantogranuloma juvenil: una entidad con amplio espectro clínico.

Juvenile xanthogranulomas (JXGs) are rare, benign lesions that belong to the large group of non-Langerhans cell histiocytoses. JXG presents with 1 or more erythematous or yellowish nodules that are usually located on the head or neck. Most JXG lesions are congenital or appear during the first year of life. Extracutaneous involvement is rare, but the literature traditionally suggests investigating the possibility of ocular compromise. JXG is mainly a clinical diagnosis, but a skin biopsy may sometimes be needed for confirmation. JXGs on the skin are self-limiting and usually do not require treatment. This review describes the clinical and therapeutic aspects of JXG, emphasizing available evidence and the diagnosis of extracutaneous involvement.

Interarm blood pressure measurement and the reference-arm assignment variability.

OBJECTIVE: The arm with the higher blood pressure (BP) is assigned as the follow up arm for hypertensive patients (reference-arm). We evaluated the reproducibility of this assignment. METHODS: BP was measured simultaneously on both arms with a double cuff validated device in two visits separated <10 days (two sets of three readings per visit). Two reference-arms were assigned in each visit (the arm with higher BP, at least ≥1 mmHg). The intravisit and intervisit agreements of this assignment were evaluated. RESULTS: We included 313 hypertensive patients. First visit mean right arm BP was 131.6 (16.6)/75.3 (9.4) mmHg and left arm BP was 132.4 (16.9)/75.7 (9.7) mmHg (P = 0.002). Intravisit concordance at the first and second visits were κ = 0.60 [95% confidence interval (CI), 0.516-0.696] and κ = 0.45 [95% CI, 0.356-0.555], respectively. Therefore, 21.8% of patients (at the first visit) and 29.1% (at the second visit) with the right arm as the reference-arm in the first round of readings changed to the left arm in the same visit in the second round of readings. The intervisit κ index was 0.25 [95% CI, 0.147-0.365]. After that, 36.8% of patients with the right arm as the reference-arm at the first visit changed to the left arm at the second visit. The subgroup (9.5%) with an interarm systolic BP difference ≥10 mmHg at the first visit did not differ significantly from the rest of patients. CONCLUSION: The reference-arm assignment agreement is weak to moderate. The assignment of the reference-arm should be individualized and not considered as definitive.

Multi-antigenic recombinant subunit vaccine against Lawsonia intracellularis: The etiological agent of porcine proliferative enteropathy.

Proliferative enteropathy, caused by Lawsonia intracellularis, represents a threat for swine industry. Current vaccines are effective but difficult to obtain and scaled up, because of demanding bacterial culture conditions. In this work, a subunit vaccine candidate against L. intracellularis was developed and its efficacy was evaluated in vivo, alone or co-formulated with pig recombinant IFN-α. The vaccine formulation contains three chimeric antigens: two outer membrane proteins and a secreted one, which were engineered by adding T epitopes using bioinformatics tools. After simultaneously expressing the three antigens in E. coli, its immunogenicity was tested in mice and pigs. Antigens co-formulated with porcine IFN-α were also assayed in the last species. Immune response was assessed by ELISA and qPCR, and histopathological studies of intestinal epithelial tissue were performed after challenge. Mice and pigs showed an increased IgG response against chimeric antigens. Particularly, there were significant differences in the antibody response when porcine IFN-α was co-administrated with L. intracellularis antigens. Besides, mRNAs from il12 and cd4 marker were detected during the first week after immunization of pigs, suggesting a Th1-type cellular immune response. The significant enhancement of oas2 gene expression indicates the effect exerted by porcine IFN-α. Post-mortem histopathological analysis post-challenge revealed damage only into epithelial cells of the gastrointestinal tract from animals of the negative control group. Injuries were related to atrophy of the intestinal villi, where a decrease of globet cells and a greater migration of lymphocytes were observed. Overall, our results demonstrated that the vaccine candidate elicited significant humoral and cellular immune responses. Besides, histopathological analysis suggested that vaccinated animals were protected against experimental L. intracellularis infection. This research constitutes a step forward to the generation of the first recombinant chimeric vaccine against L. intracellularis, representing a faster, easier and cost effective approach to counteract the porcine proliferative enteropathy.